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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2010-5-20
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pubmed:abstractText |
Recent reports indicate that (-)-epicatechin can exert cardioprotective actions, which may involve endothelial nitric oxide synthase (eNOS)-mediated nitric oxide production in endothelial cells. However, the mechanism by which (-)-epicatechin activates eNOS remains unclear. In this study, we proposed to identify the intracellular pathways involved in (-)-epicatechin-induced effects on eNOS, using human coronary artery endothelial cells in culture. Treatment of cells with (-)-epicatechin led to time- and dose-dependent effects that peaked at 10 minutes at 1 mumol/L. (-)-Epicatechin treatment activates eNOS via serine 633 and serine 1177 phosphorylation and threonine 495 dephosphorylation. Using specific inhibitors, we have established the participation of the phosphatidylinositol 3-kinase pathway in eNOS activation. (-)-Epicatechin induces eNOS uncoupling from caveolin-1 and its association with calmodulin-1, suggesting the involvement of intracellular calcium. These results allowed us to propose that (-)-epicatechin effects may be dependent on actions exerted at the cell membrane level. To test this hypothesis, cells were treated with the phospholipase C inhibitor U73122, which blocked (-)-epicatechin-induced eNOS activation. We also demonstrated inositol phosphate accumulation in (-)-epicatechin-treated cells. The inhibitory effects of the preincubation of cells with the calmodulin-dependent kinase II (CaMKII) inhibitor KN-93 indicate that (-)-epicatechin-induced eNOS activation is at least partially mediated via the Ca(2+)/CaMKII pathway. The (-)-epicatechin stereoisomer catechin was only partially able to stimulate nitric oxide production in cells. Together, these results strongly suggest the presence of a cell surface acceptor-effector for the cacao flavanol (-)-epicatechin, which may mediate its cardiovascular effects.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-10048796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-10690325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-10917931,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-11340086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-11397791,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-11399940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-12372846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-12489789,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-15304551,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-15840005,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-16418281,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-16574779,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-16790523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-16839566,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-17278969,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-18567705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-19051188,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-19101751,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-19289648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-19497380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-19537788,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20404222-19727602
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1524-4563
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
55
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1398-405
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:20404222-Adult,
pubmed-meshheading:20404222-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:20404222-Catechin,
pubmed-meshheading:20404222-Caveolins,
pubmed-meshheading:20404222-Cells, Cultured,
pubmed-meshheading:20404222-Coronary Vessels,
pubmed-meshheading:20404222-Endothelial Cells,
pubmed-meshheading:20404222-Humans,
pubmed-meshheading:20404222-Male,
pubmed-meshheading:20404222-Middle Aged,
pubmed-meshheading:20404222-Nitric Oxide,
pubmed-meshheading:20404222-Nitric Oxide Synthase Type III,
pubmed-meshheading:20404222-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:20404222-Probability,
pubmed-meshheading:20404222-Reference Values,
pubmed-meshheading:20404222-Sampling Studies,
pubmed-meshheading:20404222-Signal Transduction
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pubmed:year |
2010
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pubmed:articleTitle |
(-)-epicatechin activation of endothelial cell endothelial nitric oxide synthase, nitric oxide, and related signaling pathways.
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pubmed:affiliation |
Department of Medicine, University of California, San Diego, Calif, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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